By: Patrick Brown, 2nd year PhD candidate in the Biomedical Sciences Graduate Program
In Part I of my discussion of DNA and epigenetics, I described how DNA is first converted into mRNA via transcription, then mRNA is translated into protein. Once proteins are made from this genetic code, they can begin doing work in cells.
I ended the last article with the question: how does the body choose which genes are expressed in which cells? Here I will discuss the concept of epigenetics and its role in shaping protein expression.
We can see the effects of epigenetics all around us. Many proteins are expressed differently between males and females – these proteins are under epigenetic control. If epigenetic marks are abnormal, then certain cancers become more prevalent. The most visible difference in epigenetic marks is seen in the coat color of the agouti mouse. Each mouse pictured (above) is genetically identical, but contains different amounts of a specific epigenetic mark. How can they have the same genes, but have different coat colors?
The DNA base patterns that make up a person’s genome are inherited from one’s parents. Epigenetics is the study of the inherited characteristics of DNA that are not found in the base code. To appreciate this difference, we have to understand what DNA looks like inside of a cell. If it were stretched, then the length of DNA in each human cell would be roughly 6 feet long! However, it is compacted into a space so small that it cannot be seen without a microscope. How does it all fit?
DNA first gets wrapped around protein clusters called nucleosomes and then multiple nucleosomes clump together. When nucleosomes are compacted tightly, it is difficult for mRNA to be made, and therefore subsequent protein is not produced. However, when nucleosomes are further apart, mRNA and protein can be made relatively easily. It is these inherited epigenetic marks that control nucleosome organization.
Epigenetic marks are small chemical modifications that can be made directly to a DNA base or to nucleosome proteins. If one takes into account the types and locations of these chemical modifications, then there are roughly 40 different epigenetic marks. They function to modulate nucleosome compaction – some open it while others close it. Marks that open the DNA are termed “active” and marks that close DNA are termed “repressive”. In this way, epigenetic marks control which parts of the DNA code are converted into mRNA and ultimately protein.
A popular metaphor is to think of DNA as a piano. Each key on the piano is one gene. The pianist is the cell’s transcription and translation machinery, but to know which keys to press or genes to translate the pianist must read the sheet music – or the epigenetic marks.
Epigenetic marks are not fixed and can be placed and removed depending on the needs of the cell. As was mentioned in the last article, different cell types require expression of different proteins. A protein like insulin will have active marks along its gene in pancreatic cells, but repressive marks along its gene in cells that don’t produce insulin, such as skin cells. Moreover, the needs of a cell can change over time. As you may be aware, embryos contain stem cells – which can become any type of cell in the body. As time progresses, their cell fates become more and more restricted. At each interval the cell requires different proteins to be expressed and modulates epigenetic marks on DNA to produce the proteins needed.
To summarize, from DNA the cell produces mRNA and then protein. Proteins perform various important functions throughout the cell and are essential for life. But not all cells require the same proteins. To determine which proteins to produce, active and repressive epigenetic marks coordinate conversion of DNA to mRNA. DNA and epigenetics are truly the blueprints of life.
Morgan, H. D., Sutherland, H. G. E., Martin, D. I. K. & Whitelaw, E. Epigenetic inheritance at the agouti locus in the mouse. Nat Genet 23, 314-318 (1999).
Annunziato, A. DNA packaging: Nucleosomes and chromatin. Nature Education 1 (2008).
abcam. Guide to epigentic marks | Abcam (2013).
Klinghoffer, D. Epigenetics and the “Piano” Metaphor – Evolution News & Views, (2012).
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